Non Small Cell Lung CarcinomaPhase 1/2PRISMNCT07219576
Retifanlimab and Ruxolitinib In Solid Malignancies
A Phase 1/2 study testing Ruxolitinib and Retifanlimab in people with Non Small Cell Lung Carcinoma and Renal Cell Carcinoma, run by University of California, San Diego at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn what dose of ruxolitinib can be given safely together with retifanlimab in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Non Small Cell Lung Carcinoma, Renal Cell Carcinoma
- What is being tested?
- Ruxolitinib and Retifanlimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2026to Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Advanced or metastatic clear cell renal cell carcinoma or non-small cell lung carcinoma having progressed on prior PD-1/PD-L1 therapy (radiographic progression within 6 months of discontinuing immunotherapy; immunotherapy does not need to be the immediate line of preceding therapy).
- Decline standard of care treatment or no available standard of care treatment.
- Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Adequate organ and marrow function:
- Absolute neutrophil count ≥ 1.0×10^9/L.
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- Platelet count ≥ 100×10^9/L.
- Hemoglobin level ≥ 8.5 g/dL; criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks.
- Serum creatinine ≤ 2 mg/dL (or estimated creatinine clearance ≥ 30 mL/minute calculated by the Cockcroft Gault or Modification of Diet in Renal Disease formulas).
- Aspartate Aminotransferase and Alanine Aminotransferase ≤ 2.5 x upper limit of normal.
- Bilirubin ≤1.5 x upper limit of normal.
- Ability to take oral medication and be willing to adhere to the study intervention.
- Willingness to comply with all study procedures and availability for the duration of the study.
Who cannot join
- Pregnancy or lactation.
- No prior treatment with Janus kinase inhibitors.
- No more than one prior line of PD-1/PD-L1 therapy. No limit on prior lines of systemic therapy. PD-1/PD-L1 therapy does not need to be the most immediate prior line of therapy. Patients with progressive disease as best response to prior PD-1/PD-L1 therapy are not eligible. Need to have either stable disease, partial response, or complete response as best response using RECIST version 1.1 principles to prior PD-1/PD-L1 therapy.
- Received systemic anti-cancer therapy within 3 weeks of enrollment or small molecule kinase inhibitors within two weeks or six elimination half-lives of enrollment, whichever is sooner.
- Has received prior radiotherapy within one week before enrollment.
- Has had history of major surgery less than two weeks before enrollment. Adequate wound healing after major surgery must be assessed clinically.
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- Failure to recover from any immune related adverse event from prior immunotherapy to Common Terminology Criteria in Adverse Event grade ≤ 1 (participants with grade ≤ 2 sensory neuropathy, endocrinopathies controlled by hormone replacement, or other grade ≤ 2 not constituting a safety risk based on investigator's judgment are eligible).
- Known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate, provided they are clinically stable and without the requirement of steroid treatment for at least 14 days prior to enrollment.
- Known active or history of autoimmune disease that requires steroids or immunosuppressive agents. Patients are allowed in the study if they have vitiligo, type 1 diabetes mellitus, controlled asthma; residual hypo- or hyperthyroidism due to an autoimmune condition not requiring immunosuppressive treatment; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without steroids or immunosuppressive agents; or arthritis that is managed without systemic therapy beyond oral acetaminophen and non-steroidal anti-inflammatory drugs.
- Diagnosis of immunodeficiency or receiving systemic steroid therapy (equivalent of prednisone > 10 mg daily) or any other form of immunosuppressive therapy within seven days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids is permitted. Intra-articular, intra-ocular, intra-nasal, inhalation and ocular steroids are permitted.
- Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 7 days before first dose of study treatment.
- Active tuberculosis.
- Active immunodeficiency virus (HIV) infection. To be enrolled, patients with history of HIV must have an undetectable viral load at screening.
- Active hepatitis B or hepatitis C virus infections. To be enrolled, patients with a history of these infections must have been treated and cured with undetectable viral load at screening.
- Have clinically significant cardiovascular disease defined as:
- Cerebral vascular accident/stroke or myocardial infarction (<6 months prior to enrollment)
- Unstable angina, congestive heart failure exacerbation (New York Heart Association Classification ≥ Class II), or unstable cardiac arrhythmia (< 3 months prior to enrollment). Stable cardiac arrhythmia (such as atrial fibrillation, atrial flutter) controlled on or off medications is permitted.
- Known additional malignancy that is progressing or has required active treatment within the past 2 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, low grade prostate cancer, carcinoma in situ (e.g., breast carcinoma in situ, bladder carcinoma in situ) that have undergone potentially curative therapy or are on active surveillance are not excluded. Patients with cancer not detectable on imaging, not receiving active treatment, and not expected to impact 5-year life expectancy are eligible to enroll.
- Unable to swallow orally administered medication intact or has a history or current evidence of a gastrointestinal disorder (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis, gastrectomy, partial bowel obstruction, malabsorption) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption and metabolism of oral medications.
- History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than their primary malignancy, that in the opinion of the investigator would pose a risk to patient safety or interfere with study evaluations, procedures, or completion.
- Known allergy or hypersensitivity to any component or formulation components of retifanlimab and ruxolitinib.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Diego Moores Cancer Center
La Jolla, California, 92093
Alexandrea Cronin, (858) 822-5354, cancerCTO@health.ucsd.edu
Rana McKay, MD
About this study
Official title: PRISM: Phase 1b of Retifanlimab and Ruxolitinib In Solid Malignancies Progressing on Prior Checkpoint Inhibition
The goal of this clinical trial is to learn what dose of ruxolitinib can be given safely together with retifanlimab in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma.
The main question it aims to answer is:
What is the maximum dose of ruxolitinib that can be used safely in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma, and will it work?
Participants will:
Take drug ruxolitinib twice a day and keep a diary of when they take ruxolitinib at home; visit the clinic for infusions of retifanlimab every 4 weeks; visit the clinic for checkups and tests.
Read the detailed description
The treatment landscape for renal cell carcinoma has evolved significantly with the use of immunotherapy. Immune checkpoint inhibitors are now used in both adjuvant and metastatic settings. Programmed cell death protein-1 (PD-1) inhibitors are utilized as adjuvant therapy following nephrectomy for high-risk disease, and in the metastatic setting as first-line treatment in combination with either cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition or vascular endothelial growth factor (VEGF) pathway blockade. Despite improvements in overall survival with these approaches, the majority of patients develop either intrinsic or acquired resistance, necessitating subsequent therapy. The optimal management of patients progressing on immunotherapy remains an important unmet need in renal cell carcinoma.
Also the therapeutic landscape for non-small cell lung cancer has been transformed by immunotherapy, with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors now established as standard first-line therapy either as monotherapy for patients with high PD-L1 expression (≥50%) or in combination with chemotherapy regardless of PD-L1 status. Despite significant improvements in survival outcomes, most patients eventually develop resistance to PD-1/PD-L1 blockade. The optimal approach for non-small cell lung cancer progressing on immunotherapy remains unclear. The identification of effective treatment strategies for patients with immunotherapy-resistant non-small cell lung cancer represents a critical unmet need, particularly given the large patient population affected by this disease.
Ex vivo experiments by the investigators showed that Janus kinase inhibitors restore cytokine production and proliferation of exhausted T cells and that the Janus kinase 1/2 inhibitor ruxolitinib enhanced the efficacy of immune checkpoint inhibitors in cancer models. Also a preliminary clinical trial by the investigators showed encouraging results, inasmuch 10 of 19 evaluable patients responded to therapy with the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker nivolamab. Among the patients who responded, six had complete responses and additional two experienced an indeterminate response or stable disease.
Building on previous clinical trials, the investigators plan to use the Janus kinase 1/2 inhibitor ruxolitinib in combination with the PD-1 blocker retifanlimab in renal cell carcinoma and non-small cell lung cancer, two tumor types in which PD-1 blockers are effective at least in a subset of patients.
- Being tested
- Ruxolitinib, Retifanlimab
- Keywords
- programmed death ligand-1 blocker, Janus kinase inhibitor, 3+3 dose escalation design, recommended phase 2 dose
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakafi, Jakavi
Janus kinase 1/2 inhibitor
RetifanlimabDrug
Also called Zynyz
Programmed cell death protein-1 blocker
| Study group | Role | What they receive |
|---|---|---|
| ruxolitinib plus retifanlimab | Experimental | Combination of the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker retifanlimab. The study utilizes a standard 3+3 dose escalation design evaluating 2 dose escalation levels (15 mg and 20 mg orally twice daily) and 2 dose de-escalation levels (10 mg and 5 mg orally twice daily, if necessary) of ruxolitinib with fixed dose retifanlimab (500 mg intravenously every 4 weeks), followed by an expansion cohort at the recommended phase 2 dose. Receives: Drug: Ruxolitinib; Drug: Retifanlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose
Determine the recommended phase 2 dose of ruxolitinib in combination with a fixed dose of retifanlimab. The recommended phase 2 dose will be determined by assessment of the dose limiting toxicities during the first cycle of treatment.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2025
- Study start8 Jan 2026
- Primary completionDec 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Principal investigator, Rana Mckay, University of California, San Diego
- Investigators
- Rana McKay, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07219576
- Sponsor's protocol ID
- 812209
- Acronym
- PRISM
- Status last verified
- Jan 2026
- First submitted
- 20 Oct 2025
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRISM: Phase 1b of Retifanlimab and Ruxolitinib In Solid Malignancies Progressing on Prior Checkpoint Inhibition
- ClinicalTrials.gov ID
- NCT07219576
- Acronym / sponsor ID
- PRISM / 812209
- Keywords
- programmed death ligand-1 blocker, Janus kinase inhibitor, 3+3 dose escalation design, recommended phase 2 dose
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 8 Jan 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 22 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn what dose of ruxolitinib can be given safely together with retifanlimab in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma.
The main question it aims to answer is:
What is the maximum dose of ruxolitinib that can be used safely in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma, and will it work?
Participants will:
Take drug ruxolitinib twice a day and keep a diary of when they take ruxolitinib at home; visit the clinic for infusions of retifanlimab every 4 weeks; visit the clinic for checkups and tests.
Detailed description
The treatment landscape for renal cell carcinoma has evolved significantly with the use of immunotherapy. Immune checkpoint inhibitors are now used in both adjuvant and metastatic settings. Programmed cell death protein-1 (PD-1) inhibitors are utilized as adjuvant therapy following nephrectomy for high-risk disease, and in the metastatic setting as first-line treatment in combination with either cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition or vascular endothelial growth factor (VEGF) pathway blockade. Despite improvements in overall survival with these approaches, the majority of patients develop either intrinsic or acquired resistance, necessitating subsequent therapy. The optimal management of patients progressing on immunotherapy remains an important unmet need in renal cell carcinoma.
Also the therapeutic landscape for non-small cell lung cancer has been transformed by immunotherapy, with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors now established as standard first-line therapy either as monotherapy for patients with high PD-L1 expression (≥50%) or in combination with chemotherapy regardless of PD-L1 status. Despite significant improvements in survival outcomes, most patients eventually develop resistance to PD-1/PD-L1 blockade. The optimal approach for non-small cell lung cancer progressing on immunotherapy remains unclear. The identification of effective treatment strategies for patients with immunotherapy-resistant non-small cell lung cancer represents a critical unmet need, particularly given the large patient population affected by this disease.
Ex vivo experiments by the investigators showed that Janus kinase inhibitors restore cytokine production and proliferation of exhausted T cells and that the Janus kinase 1/2 inhibitor ruxolitinib enhanced the efficacy of immune checkpoint inhibitors in cancer models. Also a preliminary clinical trial by the investigators showed encouraging results, inasmuch 10 of 19 evaluable patients responded to therapy with the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker nivolamab. Among the patients who responded, six had complete responses and additional two experienced an indeterminate response or stable disease.
Building on previous clinical trials, the investigators plan to use the Janus kinase 1/2 inhibitor ruxolitinib in combination with the PD-1 blocker retifanlimab in renal cell carcinoma and non-small cell lung cancer, two tumor types in which PD-1 blockers are effective at least in a subset of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ruxolitinib plus retifanlimab | Experimental | Drug: Ruxolitinib, Drug: RetifanlimabCombination of the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker retifanlimab. The study utilizes a standard 3+3 dose escalation design evaluating 2 dose escalation levels (15 mg and 20 mg orally twice daily) and 2 dose de-escalation levels (10 mg and 5 mg orally twice daily, if necessary) of ruxolitinib with fixed dose retifanlimab (500 mg intravenously every 4 weeks), followed by an expansion cohort at the recommended phase 2 dose. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Advanced or metastatic clear cell renal cell carcinoma or non-small cell lung carcinoma having progressed on prior PD-1/PD-L1 therapy (radiographic progression within 6 months of discontinuing immunotherapy; immunotherapy does not need to be the immediate line of preceding therapy).
- Decline standard of care treatment or no available standard of care treatment.
- Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Adequate organ and marrow function:
Key exclusion criteria (21 listed)
- Pregnancy or lactation.
- No prior treatment with Janus kinase inhibitors.
- No more than one prior line of PD-1/PD-L1 therapy. No limit on prior lines of systemic therapy. PD-1/PD-L1 therapy does not need to be the most immediate prior line of therapy. Patients with progressive disease as best response to prior PD-1/PD-L1 therapy are not eligible. Need to have either stable disease, partial response, or complete response as best response using RECIST version 1.1 principles to prior PD-1/PD-L1 therapy.
- Received systemic anti-cancer therapy within 3 weeks of enrollment or small molecule kinase inhibitors within two weeks or six elimination half-lives of enrollment, whichever is sooner.
- Has received prior radiotherapy within one week before enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibAlso: Jakafi, JakaviJanus kinase 1/2 inhibitor | Drug | ruxolitinib plus retifanlimab |
| RetifanlimabAlso: ZynyzProgrammed cell death protein-1 blocker | Drug | ruxolitinib plus retifanlimab |
Primary outcome
Recommended phase 2 dose
Time frame: 28 days
Determine the recommended phase 2 dose of ruxolitinib in combination with a fixed dose of retifanlimab. The recommended phase 2 dose will be determined by assessment of the dose limiting toxicities during the first cycle of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rana McKay principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ruxolitinib and Retifanlimab in people with Non Small Cell Lung Carcinoma and Renal Cell Carcinoma, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rana McKay, MD ((858) 822-5354, cancerCTO@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.